We will rigorously establish the accurate chemical basis for the novel genetic scheme proposed by us and Wiener et al. of the interrelation and biosynthesis of the human M and N blood group-specific determinants. We will employ classical chemical procedures (periodate oxidation, methylation) for the full characterization of the blood M- and N-specific oligosaccharides obtained by us from alpha 1-glycopeptide. We will also use biosynthesis since we obtained with H. Schachter of Toronto promising initial results: Transformation of Tn to T and of T to N and M antigens (the latter only by sialyltransferase-containing sera of blood group MM or MN persons). We will isolate by immunochemical procedures and affinity chromatography the biosynthetic products. We will also use the sera of persons with genetic defects of their M N antigens. Because of close genetic linkage between MN and Ss we will use sera from persons of all MNSs combinations including donors who are S- and s-negative. M and N antigens occasionally are expressed in different strengths and we have found O-N-diacetyl-neuraminic acids as components of N and M. We will investigate with R. Schauer, Bochum, if there is a difference in O-acetylated sialic acid in antigens from M versus N persons and among persons with antigens of different strength. We found T antigen, a precursor of MN antigens, in malignant human glandular tissues but not in benign or healthy glands, whereas the MN antigens were present in both benign and malignant glands. T-specificity is thus carcinoma-associated. We plan to correlate the M, N and T specific structures on these glands to those on the human red cells. We will isolate the M- and N-specific structures from the glands to establish the general nature of the molecules (glycoprotein or glycolipid or both) and assess the immunochemical and chemical basis for the specificities of their immunodominant groups. We will also determine if quantity and quality of M and N specific structures in malignant gland tissue differ from those in normal glands and in benign tumors, and the relationship of the T-specific substances in malignant tissues to their MN antigens.